The long term objectives of this project are to understand the basic chiral recognition process between two molecules. The focus is on new macrocyclic host molecules, while the guest molecules are generally pharmacologically active compounds. The results of this project translate directly to the development of safer and more effective medicines as well as a much better understanding of their disposition and action. The specific aims of this proposed project are quite simple. They are as follows: (l) introduce and develop a completely new class of chiral selectors based on specific macrocyclic antibiotics and their derivatives. (2) Develop a basic understanding of the enantioselective molecular interactions between specific macrocyclic antibiotics and chiral guest molecules. (3) Use the developed mechanistic insights to explain why these particular chiral selectors (in solution) appear to produce separations with far greater selectivity and efficiency (in capillary electrophoresis and LC) than cyclodextrins, micelles and proteins, and (4) evaluate our understanding of the enantioselective interactions by testing predictive capabilities for untried separations and in designing potential second generation selectors.